Working the Kinks out of DNA Sequencing

For Dr. Robert Riehn, sequencing DNA could be as easy as sucking spaghetti through a straw. That bizarre image is how the assistant professor of physics in the College of Physical and Mathematical Sciences describes his research to unwind the genetic molecule for easier analysis. But the unexpected is to be expected from this young German physicist who is more interested in solving medical problems than following in Einstein’s footsteps.

“If I learn about the biology of molecules while studying their physical properties, maybe I can develop a better way to analyze them that will help other researchers.”

After earning a degree in South Africa, Riehn studied polymers for his doctorate at Cambridge and continued with biological research while working at Princeton. He landed at NC State a year ago after seeking out schools conducting both biotechnology and nanotechnology research. “For me,” he says, “it doesn’t have to involve quantum mechanics to be physics.”

Riehn has already come up with a novel way to study DNA with nanofluidic channels. Using electron-beam lithography, he etches an 80-nanometer-diameter channel in a piece of silica, and then fuses another piece of glass on top to create a tunnel. Once the tunnel is filled with fluid, an electric field is applied, pulling a DNA molecule, which is naturally negatively charged, into the tunnel from one end. “With DNA, everything happens according to base pairs. But because polymers like to coil up, DNA ends up looking like a plate of spaghetti, making base pairs hard to locate,” he says. “By stretching DNA into a nanochannel, we can study base pairs and determine how genes are expressed.”

Researchers previously stuck DNA onto a surface for studying after untangling it. Riehn says nanochannels are a better system because they give the molecule some wiggle room for slight expanding and contracting, providing a more accurate representation over a series of tests.

With his system in place, the physicist hopes to do more biological studies on DNA. He recently won a two-year National Human Genome Research Institute grant to measure the electrical signals of base pairs—possibly a faster and less expensive sequencing technique. Riehn also plans to use enzymes that cut DNA at specific places to learn how bacteria are able to adjust their genetic make-up to fit changing conditions. And he wants to study cancer cells to find how various genetic controls are switched on and off. “If I learn about the biology of molecules while studying their physical properties,” he says, “maybe I can develop a better way to analyze them that will help other researchers.

Dr. Robert Riehn etches nanoscale channels in silica so he can uncoil DNA molecules for easier gene sequencing and study of
base pairs.

This image shows how a DNA molecule is forced to stretch out inside a nanofluidic channel.